Registration Dossier

Administrative data

Endpoint:
acute toxicity: other routes
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well documented study report.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Principles of method if other than guideline:
single intraperitoneal injection with 14-day postobservation period
GLP compliance:
no
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Pigmentgelb HNN 79/195
- Physical state: solid, yellow
- Analytical purity: 88 %
- Impurities (identity and concentrations): 10 % 2-cyano-2-[2,3-dihydro-3-oxo-1H-isoindol-1-ylidene]-N-methylacetamide
- Stability: At least 2 years under normal conditions

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr. K. Thomae GMBH, Biberach, Germany
- Age at study initiation: 12 weeks
- Mean weight at study initiation: 170 g (males), 180 g (females)
- Fasting period before study: 16 hours before administration, but water is available ad libitum.
- Housing: 5 per cage, Stainless steel wire mesh cages, type DK-III
- Diet (e.g. ad libitum): Ssniff R; FA. SSNIFF, Soest, Germany
- Water: Demineralized water each workday, tap water on holidays; ad libitum
- Acclimation period: at least 1 week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-26
- Humidity (%): 45-75
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
0.5% aqueous CMC-solution
Details on exposure:
VEHICLE
- Concentration in vehicle: 20 % in 0.5% aqueous carboxymethyl cellulose

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weighing: before administration, then on days 3, 7 and 13;
cageside observations: < 15', 15', 30', 1 h, 2 h, 4 h and 5 h after administration of the test substance and then once each workday.
Check for moribund and dead animals twice each workday and once on holidays.
- Necropsy of survivors performed: yes, withdrawal of food 16 houre before sacrifice; necropsy with gross-pathological examination.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality.
Mortality:
No mortality observed.
Clinical signs:
Males and females: Dyspnea, apathy, staggering, tonus with stretching, urine yellow/orange, poor general state
Females: Additionally, piloerection
Body weight:
The body weight of the animals showed no adverse effects in comparison with that of the control.
Mean body weight (male / female)
- Before the study
Treatment group: 185 / 170
- After 3 days
Treatment group: 194 / 180
- After 7 days
Treatment group: 213 / 216
- After 13 days
Treatment group: 225 / 264
Control: 367 / 249
Gross pathology:
Sacrificed animais (male and female): abdominal organs, particularly Glisson's capsule, severely stained by the test substance; focal adhesions of the lobes of the liver to each other, in some cases with rounding of the margins of the liver.
Other findings:
No other findings.

Applicant's summary and conclusion